title: Genotype and phenotype in Parkinson's disease: lessons in heterogeneity from deep brain stimulation.
abstract: Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD. The consequent genetic subgroups of patients were compared with respect to phenotype, levodopa (l-dopa), and DBS responsiveness. An unprecedented number (29%) of patients tested positive for at least 1 of the currently known PD genes. Patients with Parkin mutations presented at the youngest age but had many years of disease before needing DBS, whereas glucocerebrosidase (GBA) mutation carriers reached the threshold of needing DBS earlier, and developed earlier cognitive impairment after DBS. DBS cohorts include large numbers of gene positive PD patients and can be clinically instructive in the exploration of genotype-phenotype relationships.
authors.affiliation: Sobell Department of Motor Neuroscience, University College London (UCL) Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Aikaterina
authors.initials: A
authors.lastname: Angeli
authors.forename: Niccolo E
authors.initials: NE
authors.lastname: Mencacci
authors.forename: Raquel
authors.initials: R
authors.lastname: Duran
authors.forename: Iciar
authors.initials: I
authors.lastname: Aviles-Olmos
authors.forename: Zinovia
authors.initials: Z
authors.lastname: Kefalopoulou
authors.forename: Joseph
authors.initials: J
authors.lastname: Candelario
authors.forename: Sarah
authors.initials: S
authors.lastname: Rusbridge
authors.forename: Jennifer
authors.initials: J
authors.lastname: Foley
authors.forename: Priyanka
authors.initials: P
authors.lastname: Pradhan
authors.forename: Marjan
authors.initials: M
authors.lastname: Jahanshahi
authors.forename: Ludvic
authors.initials: L
authors.lastname: Zrinzo
authors.forename: Marwan
authors.initials: M
authors.lastname: Hariz
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Patricia
authors.initials: P
authors.lastname: Limousin
authors.forename: Tom
authors.initials: T
authors.lastname: Foltynie
mesh_terms: D000328:Adult; D017668:Age of Onset; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002648:Child; D046690:Deep Brain Stimulation; D015259:Dopamine Agents / Q000627:therapeutic use; D005091:Exons / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005962:Glucosylceramidase
keywords: Parkinson's disease; deep brain stimulation; genetics; heterogeneity; phenotype